In the last funding period, we have completed a series of critical studies to examine the effect of lithotripter beam size on stone comminution, to compare the characteristics of electromagnetic (EM) vs. electrohydraulic (EH) shock wave lithotripters both in vitro and in vivo, and to develop technical innovations that can be upgraded on a modern EM lithotripter. A new line of investigation is proposed in this renewal application, which is motivated by the recognition that over the past decade, the landscape in shock wave lithotripsy (SWL) has shifted from EH to EM technology because of the longevity, stability and large dynamic range of pressure output offered by EM lithotripters. However, despite these advantages the performance of EM lithotripters (including the 3rd generation machines) has not reached the gold standard that was established by the original Dornier HM-3 (EH) lithotripter more than 25 years ago. Therefore, there is a strong desire from both lithotripter manufacturers and practicing urologists to improve the design and performance of EM lithotripters. We propose the following specific aims to develop innovative SWL technologies to be integrated in a modern EM lithotripter. Aim 1. Re-engineering the acoustic lens design in an electromagnetic shock wave lithotripter to produce an idealized pressure waveform profile with a broad beam size Aim 2. Generating a steerable and non-axisymmetric acoustic field by an electromagnetic shock wave source for better coverage of the respiratory motion of kidney stones and lateral spreading of residual fragments in vivo Aim 3. Developing co-axial microsecond tandem pulse technology in an electromagnetic shock wave lithotripter for improved stone comminution Aim 4. Optimizing treatment strategy employed during SWL to maximize stone comminution efficiency with minimal tissue injury We have assembled a multidisciplinary research team with diverse expertise in engineering, materials science, applied mathematics, and urologic surgery. We will also collaborate closely with Siemens for lithotripter design upgrade and system integration. It is anticipated that the synergistic interaction between our multidisciplinary research team and Siemens will lead to a rapid translation of basic research in academic laboratories to the next-generation commercial shock wave lithotripters that can benefit all stone patients. PUBLIC HEALTH RELEVANCE: In recent years, the prevalence of kidney stones has increased in parallel with the blistering epidemics of obesity, type 2 diabetes mellitus, and other phenotypes commonly encountered in the metabolic syndrome, and the direct expenditures for treatment of stone disease in the U.S. exceed $2 billion annually, second only to urinary tract infection among urologic diseases. Because of its non-invasive nature, ease of use, and high reimbursement rate for urologists, shock wave lithotripsy (SWL) remains a first-line therapy for the management of most kidney stones, yet the current models of clinical lithotripters have become less effective in disintegrating kidney stones, but often have higher propensity to produce tissue injury than the first- generation Dornier HM-3 lithotripter. We will carry out a multidisciplinary investigation with synergistic collaborations between academic laboratories and the medical device industry (i.e., Siemens) to develop the next-generation shock wave lithotripter with significantly improved performance and safety features that will benefit all patients that require surgical removal of kidney stones.